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11 Diseases |  |
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39 News |  |
- | LY2886721 / Eli Lilly
Journal: Human platelets release amyloid peptides ? and ? in response to haemostatic, immune, and hypoxic stimuli. (Pubmed Central) - May 24, 2023
Interestingly, the combination of hypoxia and inflammation that we simulated in vitro with reduced oxygen tension and LPS may increase the release of fibrillogenic A? and, consequently, exacerbate amyloid plaque deposition in the brain of AD patients.
- LY2886721 / Eli Lilly
BACE INHIBITION AND SYNAPTIC DYSFUNCTION: MECHANISTIC INSIGHTS FROM IPSC-DERIVED HUMAN NEURONS (EXHIBITION) - Dec 23, 2022 - Abstract #ADPD2023ADPD_1369;
BACE inhibitors are still a p recious resource to delay or prevent AD progression. Unraveling the mechanisms by which these drugs affect synaptic functionality is important for a reassessment of this treatment strategy.
- LY2886721 / Eli Lilly
EXPRESSION AND INTRACELLULAR LOCALIZATION OF Α-, Β-, AND Γ-SECRETASES, AND THE EFFECT OF THEIR INHIBITORS IN THE PERI-INFARCT ZONE IN MICE (GALLERY) - Nov 7, 2022 - Abstract #WSC2022WSC_1139;
Thus, DAPT may be considered as a potential drug for stroke therapy. This work was supported by the Ministry of Science and Higher Education of the Russian Federation (grant No.
- | sevoflurane / Generic mfg.
Journal: Beta-Site Amyloid Precursor Protein-Cleaving Enzyme Inhibition Partly Restores Sevoflurane-Induced Deficits on Synaptic Plasticity and Spine Loss. (Pubmed Central) - Jul 2, 2022
Taken together, our study suggests that sevo partly elevates BACE activity and interferes with synaptic remodeling, whereas iso mildly modulates synaptic changes in the CA1 region of the hippocampus. On the other hand, Xe does not alternate dendritic spine remodeling.
- LY2886721 / Eli Lilly
BACE INHIBITION AND SYNAPTIC DYSFUNCTION: MECHANISTIC INSIGHTS FROM HUMAN IPSC- DERIVED NEURONS () - Mar 9, 2022 - Abstract #ADPD2022ADPD_1287;
Accumulation of APP in neurons as a result of missed β-cleavage could explain synaptic dysfunction phenotype caused by pharmacological inhibition of BACE. Unraveling this mechanism is important for a reassessment of such promising treatment strategy.
- DEVELOPING BETA-SECRETASE INHIBITORS FOR TREATMENT OF ALZHEIMER’S DISEASE () - Mar 9, 2022 - Abstract #ADPD2022ADPD_1122;
The capability of BACE1 to apply such a therapeutic candidate for AD therapy has just been examined during the previous decade. There is proof indicate that the 1 inhibitor administrating time is critical and make big difference in how successful they are in curing AD.
- || Review, Journal: Selective Secretase Targeting for Alzheimer's Disease Therapy. (Pubmed Central) - Sep 17, 2021
Such therapeutic tools shall focus on slowing down or minimizing the progression of neuronal damage. Here, we summarize structures and the activities of the latest compounds designed for AD treatment, with remarkable in vitro, in vivo, and clinical phase activities.
- | LY2886721 / Eli Lilly
Preclinical, Journal: The BACE1 inhibitor LY2886721 improves diabetic phenotypes of BACE1 knock-in mice. (Pubmed Central) - Sep 12, 2021
Here, we summarize structures and the activities of the latest compounds designed for AD treatment, with remarkable in vitro, in vivo, and clinical phase activities. Our data provide support for a role of BACE1 as a regulator of systemic glucose homeostasis and suggest BACE1 inhibitors for the treatment of T2DM-associated pathologies, especially in cases where diabetes is comorbid to AD.
- || LY3202626 / Eli Lilly
Clinical, Journal: Discovery and Early Clinical Development of LY3202626, a Low-Dose, CNS-Penetrant BACE Inhibitor. (Pubmed Central) - Aug 25, 2021
LY2886721 advanced to Phase II, but development was halted due to abnormally elevated liver enzymes. Herein, we report the discovery and clinical development of LY3202626, a highly potent, CNS-penetrant, and low-dose BACE inhibitor, which successfully addressed these key development challenges.
- sirolimus / Generic mfg.
[VIRTUAL] REGULATION OF INTRACELLULAR INNATE IMMUNE AMYLOID BETA (Aβ) CLEARANCE () - Aug 2, 2021 - Abstract #AAIC2021AAIC_576;
Inhibition of Nep and BACE1 reduces 20-x peptide generation indicating this as a potential marker for Aβ. Modulation of autophagy affects 20-x peptide generation indicating the potential of targeting endo-lysosomal and autophagic pathway against AD.
- | LY2886721 / Eli Lilly, lanabecestat (AZD3293) / AstraZeneca, Eli Lilly
Journal: Partial reduction of amyloid β production by β-secretase inhibitors does not decrease synaptic transmission. (Pubmed Central) - Jun 26, 2021
Our results indicate that Aβ production can be reduced by up to 50%, a level of reduction of relevance to the protective effect of the Icelandic mutation, without causing synaptic dysfunction. We therefore suggest that future clinical trials aimed at prevention of Aβ build-up in the brain should aim for a moderate CNS exposure of BACE inhibitors to avoid side effects on synaptic function.
- ||| Aduhelm (aducanumab) / Eisai, Biogen, LY2886721 / Eli Lilly, AN1792 / Pfizer, J&J
FDA event: (2/6) Eliminating the 3 most toxic (AN-1792, Scyllo-inositol, LY2886721), 14 medications could now be submitted for FDA approval based on the new benchmark. They each reduced amyloid to an extent comparable to aducanumab. (Twitter) - Jun 9, 2021
- | LY2886721 / Eli Lilly, LY-2811376 / Eli Lilly
Journal: Preparation and biological evaluation of BACE1 inhibitors: Leveraging trans-cyclopropyl moieties as ligand efficient conformational constraints. (Pubmed Central) - Jan 28, 2021
Herein we describe the preparation and structure activity relationships (SAR) of a series of BACE1 inhibitors utilizing trans-cyclopropyl moieties as conformational constraints. The design, details of the stereochemically complex organic synthesis, and biological activity of these BACE1 inhibitors is described.
- LY2886721 / Eli Lilly
[VIRTUAL] REGULATION OF INTRACELLULAR INNATE IMMUNE AMYLOID BETA (AΒ) CLEARANCE (On Demand Symposia B) - Dec 24, 2020 - Abstract #ADPD2021ADPD_254;
We present assays for Aβ catalysis in myeloid cells (THP-1 cells and human iPSC microglia). Methods THP-1 cells were differentiated toward macrophages, and treated with various inhibitors including IDE inhibitor (6bK, Tocris), BACE inhibitor (LY2886721, Tocris), NEP inhibitor (Phosphoramidon, Tocris) and Bafilomycin (1h) before adding 100 ng/ml Aβ40 (2h), followed by 4h chase...Autophagy inhibitor BafA1 increases both 1-40 and 20-x fragments indicating the role of the endo-lysosomal system in the degradation of full length and 20-x Aβ. Conclusions We demonstrate a novel assay for Aβ degradation by Innate immune cells including THP-1 and iPSC derived microglia. Inhibition of Nep and BACE reduces 20-x peptide generation indicating this as a potential marker for Aβ clearance.
- || LY2886721 / Eli Lilly
Clinical, Journal: Pathological manifestation of the induced pluripotent stem cell-derived cortical neurons from an early-onset Alzheimer's disease patient carrying a presenilin-1 mutation (S170F). (Pubmed Central) - Apr 26, 2020
Inhibition of Nep and BACE reduces 20-x peptide generation indicating this as a potential marker for Aβ clearance. Taken together, we have established and characterized the pathological features of an AD patient carrying PS1-S170F mutation using iPSC technology, which will be the first case on this mutation and this iPSC line will serve as a useful resource for studying AD pathogenesis and drug screening in the future.
- | LY2886721 / Eli Lilly
Journal: Quantitative Analysis of F-PF-06684511, a Novel PET Radioligand for Selective β-secretase 1 Imaging, in Non-human Primate Brain. (Pubmed Central) - Mar 31, 2020
Initial brain PET measurements were performed at baseline and after oral administration of 5 mg/kg of LY2886721, a BACE1 inhibitor, in 2 cynomolgus monkeys...The effective dose of F-PF-06684511 was 0.043 mSv/MBq for humans. F-PF-06684511 is the first successful PET radioligand for BACE1 brain imaging that demonstrates favorable in vivo binding and brain kinetics in NHPs.
- LY2886721 / Eli Lilly
Melanoma-secreted amyloid beta supresses neuroinflammation and promotes brain Metastasis (Grand Ballroom B&C) - Oct 4, 2019 - Abstract #SMR2019SMR_56;
Our results demonstrate a critical role for amyloid beta in melanoma brain metastasis, establish a novel connection between brain metastasis and neurodegenerative pathologies, and show that amyloid beta is a promising therapeutic target for brain metastasis treatment. Studies to further characterize how amyloid beta acts in the melanoma brain metastasis microenvironment are currently underway.
- | LY2886721 / Eli Lilly
Trial termination: Study of LY2886721 in Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease (clinicaltrials.gov) - Jul 23, 2013
P1/2, N=128, Terminated, Sponsor: Eli Lilly and Company
Studies to further characterize how amyloid beta acts in the melanoma brain metastasis microenvironment are currently underway. Recruiting --> Terminated; Study terminated due to abnormal liver biochemical tests in some participants.
- | LY2886721 / Eli Lilly
Trial completion: A Study of LY2886721 in Healthy Participants and Participants Diagnosed With Alzheimer's Disease (clinicaltrials.gov) - May 30, 2013
P1, N=36, Completed, Sponsor: Eli Lilly and Company
Recruiting --> Terminated; Study terminated due to abnormal liver biochemical tests in some participants. Active, not recruiting --> Completed
- | LY2886721 / Eli Lilly
Trial completion: A Study of Two Dosage Forms of LY2886721 in Healthy Participants (clinicaltrials.gov) - May 22, 2013
P1, N=30, Completed, Sponsor: Eli Lilly and Company
Active, not recruiting --> Completed Active, not recruiting --> Completed
- | LY2886721 / Eli Lilly
New P1 trial: A Study of LY2886721 in Healthy Participants and Participants Diagnosed With Alzheimer's Disease (clinicaltrials.gov) - Mar 6, 2013
P1, N=36, Completed, Sponsor: Eli Lilly and Company
- | LY2886721 / Eli Lilly
New P1 trial: A Study of Two Dosage Forms of LY2886721 in Healthy Participants (clinicaltrials.gov) - Jan 23, 2013
P1, N=30, Completed, Sponsor: Eli Lilly and Company
- | LY2886721 / Eli Lilly
Trial completion: A Study of LY2886721 in Healthy Participants (clinicaltrials.gov) - Aug 8, 2012
P1, N=39, Completed, Sponsor: Eli Lilly and Company
Active, not recruiting --> Completed Active, not recruiting --> Completed
- | LY2886721 / Eli Lilly
New P1/2 trial: Study of LY2886721 in Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease (clinicaltrials.gov) - Mar 21, 2012
P1/2, N=128, Terminated, Sponsor: Eli Lilly and Company
- | LY2886721 / Eli Lilly
New P1 trial: A Study of LY2886721 in Healthy Participants (clinicaltrials.gov) - Feb 14, 2012
P1, N=39, Completed, Sponsor: Eli Lilly and Company
- LY2886721 / Eli Lilly
Trial completion: Disposition of Carbon-14-Labeled LY2886721 ([^14C]-LY2886721) Following Oral Administration in Healthy Human Participants (clinicaltrials.gov) - Aug 9, 2011
P1, N=8, Completed, Sponsor: Eli Lilly and Company
Active, not recruiting --> Completed Recruiting --> Completed